The overall objective of this proposal is to learn more about neurotransmitter receptors of insects and their ionic channels and identify any differences that may exist between them and their counterparts in vertebrates, differences that may be utilized to synthesize selective insecticides. The approach used is biochemical, and two major methods are used to identify receptors; one is the study of receptor-regulated ionic fluxes, and the other is their specific binding of radiolabeled drugs. Two kinds of insect tissues will be used: housefly brain as a source for central acetycholine, gamma-amino-butyric acid (GABA) and glutamate receptors, and housefly thorax and locust leg muscle as sources for the last two receptors. In order to identify ion transport mechanisms may be regulated by neurotransmitter receptors, a rapid quench-flow method will be used to study fluxes of 86Rb plus and 36 Cl minus into microsacs made from membranes of insect muscle and possibly brain. Thus, filter assays will be used with (3H)quinuclidinyl benzilate for identifying muscarinic receptors, (125i)alpha-bungarotoxin for nicotinic receptors, (3H)-phencyclidine for the ionic channel site of the nicotinic receptor, L-(3H)glutamate and (3H)kainic acid for glutamate receptors, (3H)GABA and (3H)muscimol for GABA receptors, and possibly (3H)flunitrazepam as a label for the diazepam-binding site that may be related to the GABA-associated Cl minus channel. Once the neurotransmitter receptors and their associated ionic channels are identified, studies will be conducted to learn more about their binding sites and how they are influenced by changes in pH, temperature and ions and by various lipids and phospholipase treatments. Finally, the effect of several groups of chemicals will be tested on these receptors and ionic channels so as to determine if a certain chemical may be a good potential selective insecticide.